Review
Environmental Sciences
Sang Hee Lee, Jongwoon Kim, Jinyong Kim, Jaehyun Park, Sanghee Park, Kyu-Bong Kim, Byung-Mu Lee, Seok Kwon
Summary: In this study, the current application status of Structure Activity Relationship (SAR)-based read-across in the Republic of Korea (ROK) was examined in terms of chemical risk assessments and registrations. The Ministry of Environment (MOE) and the Ministry of Food and Drug Safety (MFDS) are both considering the use of read-across approaches in their regulatory processes. However, the limitations of read-across, such as the lack of standardized acceptance criteria and inconsistencies in scientific evidence, must be addressed. Cooperative efforts from regulatory agencies, academia, and industry are necessary to improve the quality and acceptance of read-across data.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS
(2022)
Article
Environmental Sciences
Pietro Cozzini, Francesca Cavaliere, Giulia Spaggiari, Gianluca Morelli, Marco Riani
Summary: According to Eurostat, the production of hazardous chemicals in the EU reached 211 million tonnes in 2019, which has attracted considerable attention from the scientific community. Due to the large number of chemical compounds, it is impossible to identify all possible toxic interactions using traditional in vitro/in vivo tests. Therefore, this study uses computational approaches to screen the interactions of food contact chemicals with the nuclear receptor family, providing a cost and time-effective solution.
Article
Environmental Sciences
Byung-Mu Lee, Sang Hee Lee, Takashi Yamada, Sanghee Park, Ying Wang, Kyu-Bong Kim, Seok Kwon
Summary: This paper aimed to investigate the current status of read-across approaches in South Korea, Japan, and China in terms of applications and regulatory acceptance. Read-across is not widely used for chemical registrations in these countries and regulatory acceptance may differ among them. Considering the advantages and limitations of read-across, it is expected that read-across may soon gradually be employed in Asian countries.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2022)
Article
Environmental Sciences
Carlie A. LaLone, Donovan J. Blatz, Marissa A. Jensen, Sara M. F. Vliet, Sally Mayasich, Kali Z. Mattingly, Thomas R. Transue, Wilson Melendez, Audrey Wilkinson, Cody W. Simmons, Carla Ng, Chengxin Zhang, Yang Zhang
Summary: Computational screening using molecular modeling approaches is widely used in drug discovery. This study aimed to develop an analysis pipeline for cross-species extrapolation in chemical safety evaluation. The SeqAPASS tool and ITASSER-generated protein models were used for sequence and structural comparisons, providing evidence of conservation for toxicity extrapolation. The pipeline facilitates rapid and efficient toxicological assessments among species with limited or no existing toxicity data.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2023)
Article
Engineering, Industrial
Mark Fleming, Keri Harvey, Kate C. Bowers
Summary: The IAEA inquiry into the Fukushima nuclear disaster in 2012 identified the culture of the regulator as a contributing factor. This has led to the development of international guidelines on safety culture assessment by the IAEA and OECD. However, there is currently no psychometrically tested perception survey on regulator safety culture publicly available. This paper describes the initial testing of a perception survey developed by the IAEA working group, which supported a five-factor model.
Article
Computer Science, Theory & Methods
B. V. Raghavendra Rao, M. N. Jayalal Sarma
Summary: This paper studies the isomorphism testing problem of formulas in the Boolean and arithmetic settings. It proposes a deterministic polynomial time canonization scheme for polynomials computed by read-once arithmetic formulas. The research finds that the problem becomes polynomial-time equivalent to the graph isomorphism problem when the input formulas can be represented as OR of two or more read-once formulas.
INFORMATION AND COMPUTATION
(2022)
Article
Environmental Sciences
Luigi Margiotta-Casaluci, Stewart F. Owen, Matthew J. Winter
Summary: The extrapolation of biological data across species is essential for biomedical research and drug development. The use of comparative biology enables researchers to understand human diseases and develop safe and effective medicines. However, the presence of pharmaceuticals in the environment and the need to assess their impact on wildlife have led to increased interest in extrapolating pharmacological and toxicological data across different species. This article discusses the theoretical and experimental advancements in this field over the past decade and calls for further research on the conservation of drug targets and the quantitative relationship between target modulation and adverse effects, as well as the use of high-throughput experimental and computational approaches to predict internal exposure dynamics.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Richard K. Cross, Dave Spurgeon, Claus Svendsen, Elma Lahive, Simon Little, Frank von der Kammer, Frederic Loosli, Marianne Matzke, Teresa F. Fernandes, Vicki Stone, Willie J. G. M. Peijnenburg, Eric A. J. Bleeker
Summary: Even small changes in physicochemical properties of nanoforms (NFs) can influence their environmental fate and hazard. Testing and characterizing each individual NF will not be feasible due to the large number of new materials being developed. Targeting the most relevant form of the NF for a given exposure is important for efficient risk assessment. In aquatic systems, functional fate processes play a key role in determining the exposure relevant form of NFs. Grouping of NFs and read-across based on functional fate pathways can be justified by considering the shared fate and hazard profile. A new Integrated Approaches to Testing and Assessment (IATA) is presented, focusing on dissolution, dispersion stability, chemical transformations, and the contribution to toxicity from particles and dissolved components. This IATA can be used as a template for future in vivo kinetic assessments.
Article
Toxicology
Carine Jacques, Emilien L. Jamin, Isabelle Jouanin, Cecile Canlet, Marie Tremblay-Franco, Jean-Francois Martin, Daniel Zalko, Yves Brunel, Sandrine Bessou-Touya, Laurent Debrauwer, Pierre-Jacques Ferret, Helene Duplan
Summary: This study used metabolomics and read across methods to compare the cosmetic ingredient DIV665 with the reference compound PA102, demonstrating biological similarity in skin and liver metabolism. The findings suggest that DIV665, when applied according to consumer topical use scenario, is likely to exhibit low local skin and systemic toxicity similar to PA102.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Environmental Sciences
Sally A. Mayasich, Michael R. Goldsmith, Kali Z. Mattingly, Carlie A. LaLone
Summary: New approach methodologies (NAMs) are being developed to reduce and replace vertebrate animal testing in the field of ecotoxicology and risk assessment. In this study, the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to assess the conservation of a specific enzyme's amino acid sequence across different species, demonstrating the application of NAMs in understanding chemical interactions with protein targets. Variants of the enzyme were created through mutagenesis and tested for chemical inhibition in vitro, revealing significant differences in inhibitory concentrations. Molecular modeling and virtual docking were also performed to analyze the protein's structure and potential binding sites. The development of NAMs for evaluating chemical susceptibility across species requires consideration of various factors such as chemical characteristics, substituted amino acids, and complexity of the protein target.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2023)
Article
Toxicology
Eric March-Vila, Giacomo Ferretti, Emma Terricabras, Ines Ardao, Jose Manuel Brea, Maria Jose Varela, Alvaro Arana, Juan Andres Rubiolo, Ferran Sanz, Maria Isabel Loza, Laura Sanchez, Hector Alonso, Manuel Pastor
Summary: In order to reduce the impact of human activity on the environment, many industries in the leather and textile sector are adopting measures to characterize the chemical safety of substances commonly used in their processes. This study compiles and annotates the substances used in this sector, using a combination of data collection, experimental methods, and in silico predictions. The results show that in silico methods can provide reasonably good hazard estimations and fill knowledge gaps in the chemical space of the leather and textile industry.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
James W. Firman, Ans Punt, Mark T. D. Cronin, Alan R. Boobis, Martin F. Wilks, Paul A. Hepburn, Anette Thiel, Karma C. Fussell
Summary: The study aimed to determine the utility of high-throughput screening (HTS) data in toxicological read-across for food-relevant chemicals. Results showed that HTS data could help elucidate bioactivities, close data gaps, and define the boundaries of chemical space. The evaluation of paraben-gallates and pyranone-type compounds for estrogenicity demonstrated the potential for identifying out-of-domain compounds.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fjodor Melnikov, Lennart T. T. Anger, Catrin Hasselgren
Summary: Due to challenges with historical data and assay formats, in silico models for safety endpoints often rely on discretized data. However, these models have limitations that affect compound design. In this study, a consistent data inference approach was used to estimate IC50 for hERG inhibition. The resulting models showed high accuracy and can be valuable in pharmaceutical projects for compound ranking and evaluation against specific inhibition thresholds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
R. D. Handy, N. J. Clark, J. Vassallo, C. Green, F. Nasser, K. Tatsi, T. H. Hutchinson, D. Boyle, M. Baccaro, N. van den Brink, C. Svendsen
Summary: Little is known about the bioaccumulation potential of manufactured nanomaterials, but a meta-analysis of existing data sets on particle properties and bioaccumulation in earthworms revealed that some particle metrics could trigger bioaccumulation testing and predict nano bioaccumulation factors. Additionally, nano biomagnification factors were calculated in rainbow trout tissue, showing significant correlations with earthworm tissue nano bioaccumulation factors. These findings suggest that bioaccumulation measurements in earthworms could be predictive of values in fish, allowing for confident prediction of the bioaccumulation potential of manufactured nanomaterials based on simple particle metrics.
ENVIRONMENTAL SCIENCE-NANO
(2021)
Article
Nursing
Seung Eun Lee, V. Susan Dahinten, Jong Hyun Lee
Summary: This study aimed to test a theoretical model of the relationships between enabling factors (supervisor/clinical leader support for patient safety, hospital management support for patient safety, and psychological safety), and enacting factors of patient safety culture with nurse assessments of patient safety. The findings showed that psychological safety was associated with all enacting factors, and all enacting factors were associated with overall patient safety. Hospital management support was associated with all enacting factors except teamwork, while supervisor/clinical leader support was only associated with handoffs and information exchange, and withholding voice. Teamwork was influenced only by psychological safety.
Article
Toxicology
Alexandra Maertens, Mounir Bouhifd, Liang Zhao, Shelly Odwin-DaCosta, Andre Kleensang, James D. Yager, Thomas Hartung
ARCHIVES OF TOXICOLOGY
(2017)
Article
Toxicology
Salil N. Pendse, Alexandra Maertens, Michael Rosenberg, Dipanwita Roy, Rick A. Fasani, Marguerite M. Vantangoli, Samantha J. Madnick, Kim Boekelheide, Albert J. Fornace, Shelly-Ann Odwin, James D. Yager, Thomas Hartung, Melvin E. Andersen, Patrick D. McMullen
ARCHIVES OF TOXICOLOGY
(2017)
Article
Medicine, Research & Experimental
Thomas Luechtefeld, Alexandra Maertens, Daniel P. Russo, Costanza Rovida, Hao Zhu, Thomas Hartung
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2016)
Article
Medicine, Research & Experimental
Thomas Luechtefeld, Alexandra Maertens, Daniel P. Russo, Costanza Rovida, Hao Zhu, Thomas Hartung
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2016)
Editorial Material
Medicine, Research & Experimental
Alexandra Maertens, Bruno Hubesch, Costanza Rovida
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2016)
Article
Chemistry, Multidisciplinary
Alexandra Maertens, Hans Plugge
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2018)
Article
Toxicology
Georgina Harris, Melanie Eschment, Sebastian Perez Orozco, J. Michael McCaffery, Richard Maclennan, Daniel Severin, Marcel Leist, Andre Kleensang, David Pamies, Alexandra Maertens, Helena T. Hogberg, Dana Freeman, Alfredo Kirkwood, Thomas Hartung, Lena Smirnova
ARCHIVES OF TOXICOLOGY
(2018)
Editorial Material
Medicine, Research & Experimental
Megan Chesnut, Takashi Yamada, Timothy Adams, Derek Knight, Nicole Kleinstreuer, George Kass, Thomas Luechtefeld, Thomas Hartung, Alexandra Maertens
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2018)
Article
Genetics & Heredity
Alexandra Maertens, Vy Tran, Andre Kleensangi, Thomas Hartung
FRONTIERS IN GENETICS
(2018)
Review
Toxicology
Martin L. Stephens, Sevcan Gul Akgun-Olmez, Sebastian Hoffmann, Rob de Vries, Burkhard Flick, Thomas Hartung, Manoj Lalu, Alexandra Maertens, Hilda Witters, Robert Wright, Katya Tsaioun
TOXICOLOGICAL SCIENCES
(2019)
Article
Multidisciplinary Sciences
Alexandra Maertens, Vy P. Tran, Mikhail Maertens, Andre Kleensang, Thomas H. Luechtefeld, Thomas Hartung, Channing J. Paller
SCIENTIFIC REPORTS
(2020)
Article
Chemistry, Medicinal
Emily Golden, Mikhail Maertens, Thomas Hartung, Alexandra Maertens
Summary: Chemical respiratory sensitization is a significant immunological process that leads to health issues such as occupational asthma, but it is difficult to predict. Regulatory bodies often use the skin sensitization status of chemicals as a proxy for respiratory sensitization when assessing safety. Some models have been developed to evaluate this, but potency and data quality issues remain to be addressed.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Emily Golden, Daniel C. Ukaegbu, Peter Ranslow, Robert H. Brown, Thomas Hartung, Alexandra Maertens
Summary: In our previous work, we demonstrated 70-80% accuracies for various skin sensitization computational tools using human data. In this study, we expanded the data set using the NICEATM human skin sensitization database, resulting in a final data set of 1355 chemicals. We evaluated the performance of different computational tools and found lower accuracies compared to previous estimates, with Toxtree and OECD QSAR Toolbox achieving balanced accuracies of 63% and 65%, respectively.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Medicine, Research & Experimental
Fenna C. M. Sille, Spyros Karakitsios, Andre Kleensang, Kirsten Koehler, Alexandra Maertens, Gary W. Miller, Carsten Prasse, Lesliam Quiros-Alcala, Gurumurthy Ramachandran, Stephen M. Rappaport, Ana M. Rule, Denis Sarigiannis, Lena Smirnova, Thomas Hartung
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2020)